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Gouveia, D., Almunia, C., Cogne, Y., Pible, O., Degli-Esposti, D., Salvador, A., . . . Armengaud, J. (2019). Ecotoxicoproteomics: A decade of progress in our understanding of anthropogenic impact on the environment. Journal of Proteomics, 198, 66-77, Article ID S1874-3919(18)30423-8.
Open this publication in new window or tab >>Ecotoxicoproteomics: A decade of progress in our understanding of anthropogenic impact on the environment
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2019 (English)In: Journal of Proteomics, ISSN 1874-3919, E-ISSN 1876-7737, Vol. 198, p. 66-77, article id S1874-3919(18)30423-8Article in journal (Refereed) Published
Abstract [en]

Anthropogenic pollutants are found worldwide. Their fate and effects on human and ecosystem health must be appropriately monitored. Today, ecotoxicology is focused on the development of new methods to assess the impact of pollutant toxicity on living organisms and ecosystems. In situ biomonitoring often uses sentinel animals for which, ideally, molecular biomarkers have been defined thanks to which environmental quality can be assessed. In this context, high-throughput proteomics methods offer an attractive approach to study the early molecular responses of organisms to environmental stressors. This approach can be used to identify toxicity pathways, to quantify more precisely novel biomarkers, and to draw the possible adverse outcome pathways. In this review, we discuss the major advances in ecotoxicoproteomics made over the last decade and present the current state of knowledge, emphasizing the technological and conceptual advancements that allowed major breakthroughs in this field, which aims to “make our planet great again”.

Significance

Ecotoxicoproteomics is a protein-centric methodology that is useful for ecotoxicology and could have future applications as part of chemical risk assessment and environmental monitoring. Ecotoxicology employing non-model sentinel organisms with highly divergent phylogenetic backgrounds aims to preserve the functioning of ecosystems and the overall range of biological species supporting them. The classical proteomics workflow involves protein identification, functional annotation, and extrapolation of toxicity across species. Thus, it is essential to develop multi-omics approaches in order to unravel molecular information and construct the most suitable databases for protein identification and pathway analysis in non-model species. Current instrumentation and available software allow relevant combined transcriptomic/proteomic studies to be performed for almost any species. This review summarizes these approaches and illustrates how they can be implemented in ecotoxicology for routine biomonitoring.

Place, publisher, year, edition, pages
Elsevier, 2019
Keywords
Biomarkers, Biomonitoring, Ecotoxicology, Environmental assessment, Environmental health, Mass spectrometry, Pollutant mode of action, Proteogenomics, Proteomics, Sentinel species, Targeted proteomics
National Category
Bioinformatics and Systems Biology
Identifiers
urn:nbn:se:liu:diva-155983 (URN)10.1016/j.jprot.2018.12.001 (DOI)30529745 (PubMedID)2-s2.0-85058405842 (Scopus ID)
Available from: 2019-04-01 Created: 2019-04-01 Last updated: 2019-04-08Bibliographically approved
Rodrigues, P. M., Campos, A., Kuruvilla, J., Schrama, D. & Cristobal, S. (2017). Chapter 17 - Proteomics in Aquaculture: Quality and Safety. In: Colgrave, Michelle L. (Ed.), Proteomics in Food Science: (pp. 279-295). Elsevier
Open this publication in new window or tab >>Chapter 17 - Proteomics in Aquaculture: Quality and Safety
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2017 (English)In: Proteomics in Food Science / [ed] Colgrave, Michelle L., Elsevier, 2017, p. 279-295Chapter in book (Other academic)
Abstract [en]

Aquaculture is a growing sector of the food industry that actively tries to integrate scientific knowledge into its management strategies. Aquaculture faces several key challenges including the provision of high-quality nutritional sources that serve to address both quality and safety, thus transforming production and management strategies to integrate sustainable principles. Proteomics has been established as a powerful and unbiased instrument in environmental monitoring and risk assessment. Proteomics in aquaculture has been applied to address welfare, nutrition, health, environmental quality, and safety. In this review, we will focus on the proteomics-based method developed and implemented for its application to elucidate the key challenges that face the fish and seafood industries: quality and safety. The latest methodological developments in high-throughput proteomics and metaproteomics are seeing rapid integration into aquaculture research contributing to the common goal of offering high quality food production processes and environmental sustainability.

Place, publisher, year, edition, pages
Elsevier, 2017
Keywords
Aquaculture, Assessment, Fish, Metaproteomics, Proteomics, Safety, Seafood, Shotgun proteomics
National Category
Environmental Management
Identifiers
urn:nbn:se:liu:diva-155982 (URN)10.1016/B978-0-12-804007-2.00017-5 (DOI)2-s2.0-85040579956 (Scopus ID)9780128040072 (ISBN)
Available from: 2019-04-01 Created: 2019-04-01 Last updated: 2019-07-02Bibliographically approved
Lopes, V. R., Loitto, V., Audinot, J., Bayat, N., Gutleb, A. C. & Cristobal, S. (2016). Dose‑dependent autophagic effectof titanium dioxide nanoparticles in humanHaCaT cells at non‑cytotoxic levels. Journal of Nanobiotechnology, 14(22), 1-13
Open this publication in new window or tab >>Dose‑dependent autophagic effectof titanium dioxide nanoparticles in humanHaCaT cells at non‑cytotoxic levels
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2016 (English)In: Journal of Nanobiotechnology, ISSN 1477-3155, E-ISSN 1477-3155, Vol. 14, no 22, p. 1-13Article in journal (Refereed) Published
Abstract [en]

Background: Interactions between nanoparticles and cells are now the focus of a fast-growing area of research.Though many nanoparticles interact with cells without any acute toxic responses, metal oxide nanoparticles includingthose composed of titanium dioxide (TiO2-NPs) may disrupt the intracellular process of macroautophagy.Autophagy plays a key role in human health and disease, particularly in cancer and neurodegenerative diseases. Weherein investigated the in vitro biological effects of TiO2-NPs (18 nm) on autophagy in human keratinocytes (HaCaT)cells at non-cytotoxic levels.Results: TiO2-NPs were characterized by transmission electron microscopy (TEM) and dynamic light scatteringtechniques. Cellular uptake, as evaluated by TEM and NanoSIMS revealed that NPs internalization led to the formationof autophagosomes. TiO2-NPs treatment did not reduce cell viability of HaCaT cells nor increased oxidative stress. Cellularautophagy was additionally evaluated by confocal microscopy using eGFP-LC3 keratinocytes, western blottingof autophagy marker LC3I/II, immunodetection of p62 and NBR1 proteins, and gene expression of LC3II, p62, NBR1,beclin1 and ATG5 by RT-qPCR. We also confirmed the formation and accumulation of autophagosomes in NPs treatedcells with LC3-II upregulation. Based on the lack of degradation of p62 and NBR1 proteins, autophagosomes accumulationat a high dose (25.0 μg/ml) is due to blockage while a low dose (0.16 μg/ml) promoted autophagy. Cellularviability was not affected in either case.Conclusions: The uptake of TiO2-NPs led to a dose-dependent increase in autophagic effect under non-cytotoxicconditions. Our results suggest dose-dependent autophagic effect over time as a cellular response to TiO2-NPs. Mostimportantly, these findings suggest that simple toxicity data are not enough to understand the full impact of TiO2-NPsand their effects on cellular pathways or function.

Place, publisher, year, edition, pages
BioMed Central, 2016
Keywords
Autophagy, Cell-nanoparticle interactions, Dose, Keratinocytes, Titanium dioxide nanoparticles
National Category
Cell Biology
Identifiers
urn:nbn:se:liu:diva-126342 (URN)10.1186/s12951-016-0174-0 (DOI)000372577700001 ()27001369 (PubMedID)
Projects
Nanoimpact
Funder
Swedish Research Council, 621-2011-5267
Note

Funding agencies: Swedish Research Council-Natural Science; VR-NT; Carl Trygger Foundation; Oscar and Lilli Lamms Minne Foundation; Angpanneforening Research foundation; IKERBASQUE Basque Foundation for science; VINNOVA - County Councils of Ostergotland, Sweden; Linkoping 

Available from: 2016-03-22 Created: 2016-03-22 Last updated: 2017-11-30Bibliographically approved
Rajapakse, K., Drobne, D., Kastelec, D., Kogej, K., Makovec, D., Gallampois, C., . . . Cristobal, S. (2016). Proteomic analyses of early response of unicellular eukaryotic microorganism Tetrahymena thermophila exposed to TiO2 particles.. Nanotoxicology, 10(5), 542-556
Open this publication in new window or tab >>Proteomic analyses of early response of unicellular eukaryotic microorganism Tetrahymena thermophila exposed to TiO2 particles.
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2016 (English)In: Nanotoxicology, ISSN 1743-5390, E-ISSN 1743-5404, Vol. 10, no 5, p. 542-556Article in journal (Refereed) Published
Abstract [en]

Key biological functions involved in cell survival have been studied to understand the difference between the impact of exposure to TiO2 nanoparticles (TiO2-NPs) and their bulk counterparts (bulk-TiO2). By selecting a unicellular eukaryotic model organism and applying proteomic analysis an overview of the possible impact of exposure could be obtained. In this study, we investigated the early response of unicellular eukaryotic protozoan Tetrahymena thermophila exposed to TiO2-NPs or bulk-TiO2 particles at subtoxic concentrations for this organism. The proteomic analysis based on 2DE + nLC-ESI-MS/MS revealed 930 distinct protein spots, among which 77 were differentially expressed and 18 were unambiguously identified. We identified alterations in metabolic pathways, including lipid and fatty acid metabolism, purine metabolism and energetic metabolism, as well as salt stress and protein degradation. This proteomic study is consistent with our previous findings, where the early response of T. thermophila to subtoxic concentrations of TiO2 particles included alterations in lipid and fatty acid metabolism and ion regulation. The response to the lowest TiO2-NPs concentration differed significantly from the response to higher TiO2-NPs concentration and both bulk-TiO2concentrations. Alterations on the physiological landscape were significant after exposure to both nano- and bulk-TiO2; however, no toxic effects were evidenced even at very high exposure concentrations. This study confirms the relevance of the alteration of the lipid profile and lipid metabolism in understanding the early impact of TiO2-NPs in eukaryotic cells, for example, phagocytosing cells like macrophages and ciliated cells in the respiratory epithelium.

Place, publisher, year, edition, pages
Taylor & Francis: , 2016
Keywords
Nanotoxicology, particle toxicology, proteomics
National Category
Cell Biology
Identifiers
urn:nbn:se:liu:diva-123355 (URN)10.3109/17435390.2015.1091107 (DOI)000372756300004 ()26524663 (PubMedID)
Funder
Östergötland County CouncilCarl Tryggers foundation VINNOVASwedish Research CouncilMagnus Bergvall FoundationLars Hierta Memorial Foundation
Note

Funding agencies: Swedish Research Council-Natural Science; Carl Trygger Foundation; VINNOVA-Vinnmer program; Oscar Lilli Lamms Minne Foundation; Langmanska kulturfonden; Lars Hiertas Minne foundation; IKERBASQUE; Basque Foundation for science; Angpanneforening Research fo

Available from: 2016-01-26 Created: 2015-12-12 Last updated: 2017-11-30Bibliographically approved
Marco-Ramell, A., de Almeida, A. M., Cristobal, S., Rodrigues, P., Roncada, P. & Bassols, A. (2016). Proteomics and the search for welfare and stress biomarkers in animal production in the one health context. Molecular Biosystems, 12(7), 2024-2035
Open this publication in new window or tab >>Proteomics and the search for welfare and stress biomarkers in animal production in the one health context
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2016 (English)In: Molecular Biosystems, ISSN 1742-206X, E-ISSN 1742-2051, Vol. 12, no 7, p. 2024-2035Article, review/survey (Refereed) Published
Abstract [en]

Stress and welfare are important factors to animal production in a context of growing production optimization and scrutiny by the general public. In a context in which animal and human health are intertwined aspects of the one-health concept it is of utmost importance to define markers for stress and welfare. These are important tools for producers, retailers, regulatory agents and ultimately consumers to effectively monitor and assess the welfare state of production animals. Proteomics is the science that studies the proteins existing in a given tissue or fluid. In this review we address this topic by showing clear examples where proteomics has been used to study stress-induced changes at various levels. We adopt a multi-species (cattle, swine, small ruminants, poultry, fish and shellfish) approach under the effect of varied stress inducers (handling, transport, management, nutritional, thermal and exposure to pollutants) clearly demonstrating how Proteomics and Systems Biology are key elements to the study of stress and welfare on farm animals and a powerful tool to animal welfare, health and productivity.

Place, publisher, year, edition, pages
Royal Society of Chemistry, 2016
Keywords
proteomics, stress, biomarkers, farm animals, aquaculture
National Category
Biochemistry and Molecular Biology
Identifiers
urn:nbn:se:liu:diva-126343 (URN)10.1039/C5MB00788G (DOI)000378395000001 ()26931796 (PubMedID)
Projects
Nanoimpact
Funder
Swedish Research Council, 621-2011-5267
Available from: 2016-03-22 Created: 2016-03-22 Last updated: 2017-11-30Bibliographically approved
Campos, A., Danielsson, G., Farinha, A. P., Kuruvilla, J., Warholm, P. & Cristobal, S. (2016). Shotgun proteomics to unravel marine mussel (Mytilus edulis) response to long-term exposure to low salinity and propranolol in a Baltic Sea microcosm. Journal of Proteomics, 137, 97-106
Open this publication in new window or tab >>Shotgun proteomics to unravel marine mussel (Mytilus edulis) response to long-term exposure to low salinity and propranolol in a Baltic Sea microcosm
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2016 (English)In: Journal of Proteomics, ISSN 1874-3919, E-ISSN 1876-7737, Vol. 137, p. 97-106Article in journal (Refereed) Published
Abstract [en]

Pharmaceuticals, among them the β-adrenoreceptor blocker propranolol, are an important group of environmental contaminants reported in European waters. Laboratory exposure to pharmaceuticals on marine species has been performed without considering the input of the ecosystem flow. To unravel the ecosystem response to long-term exposure to propranolol we have performed long-term exposure to propranolol and low salinity in microcosms. We applied shotgun proteomic analysis to gills of Mytilus edulis from those Baltic Sea microcosms and identified 2071 proteins with a proteogenomic strategy. The proteome profiling patterns from the 587 highly reproductive proteins among groups define salinity as a key factor in the mussel´s response to propranolol. Exposure at low salinity drives molecular mechanisms of adaptation based on a decrease in the abundance of several cytoskeletal proteins, signalling and intracellular membrane trafficking pathway combined with a response towards the maintenance of transcription and translation. The exposure to propranolol combined with low salinity modulates the expression of structural proteins including cilia functions and decrease the expression membrane protein transporters. This study reinforces the environment concerns of the impact of low salinity in combination with anthropogenic pollutants and anticipate critical physiological conditions for the survival of the blue mussel in the northern areas.

Place, publisher, year, edition, pages
Elsevier, 2016
Keywords
Mytilus edulis, shotgun proteomics, propranolol, low salinity, environmental monitoring, climate change
National Category
Biochemistry and Molecular Biology
Identifiers
urn:nbn:se:liu:diva-124213 (URN)10.1016/j.jprot.2016.01.010 (DOI)000374368800010 ()
Funder
Swedish Research Council
Note

Funding agencies: Swedish Research Council-Natural Science; VR-NT; Carl Trygger Foundation; Oscar and Lilli Lamms Minne Foundation; Angpanneforening Research Foundation; Magnus Bergsvall Foundation; IKERBASQUE; Basque Foundation for Science; VINNOVA; County Council of Oste

Available from: 2016-01-22 Created: 2016-01-22 Last updated: 2017-11-30Bibliographically approved
Almeida, A. M., Bassols, A., Bendixen, E., Bhide, M., Ceciliani, F., Cristobal, S., . . . Turk, R. (2015). Animal board invited review: advances in proteomics for animal and food sciences. Animal, 9(1)
Open this publication in new window or tab >>Animal board invited review: advances in proteomics for animal and food sciences
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2015 (English)In: Animal, ISSN 1751-7311, E-ISSN 1751-732X, Vol. 9, no 1Article, review/survey (Refereed) Published
Abstract [en]

Animal production and health (APH) is an important sector in the world economy, representing a large proportion of the budget of all member states in the European Union and in other continents. APH is a highly competitive sector with a strong emphasis on innovation and, albeit with country to country variations, on scientific research. Proteomics (the study of all proteins present in a given tissue or fluid - i.e. the proteome) has an enormous potential when applied to APH. Nevertheless, for a variety of reasons and in contrast to disciplines such as plant sciences or human biomedicine, such potential is only now being tapped. To counter such limited usage, 6 years ago we created a consortium dedicated to the applications of Proteomics to APH, specifically in the form of a Cooperation in Science and Technology (COST) Action, termed FA1002 - Proteomics in Farm Animals: www.cost-faproteomics.org. In 4 years, the consortium quickly enlarged to a total of 31 countries in Europe, as well as Israel, Argentina, Australia and New Zealand. This article has a triple purpose. First, we aim to provide clear examples on the applications and benefits of the use of proteomics in all aspects related to APH. Second, we provide insights and possibilities on the new trends and objectives for APH proteomics applications and technologies for the years to come. Finally, we provide an overview and balance of the major activities and accomplishments of the COST Action on Farm Animal Proteomics. These include activities such as the organization of seminars, workshops and major scientific conferences, organization of summer schools, financing Short-Term Scientific Missions (STSMs) and the generation of scientific literature. Overall, the Action has attained all of the proposed objectives and has made considerable difference by putting proteomics on the global map for animal and veterinary researchers in general and by contributing significantly to reduce the East-West and North-South gaps existing in the European farm animal research. Future activities of significance in the field of scientific research, involving members of the action, as well as others, will likely be established in the future.

Place, publisher, year, edition, pages
Cambridge University Press (CUP): STM Journals, 2015
Keywords
Proteomics; farm animals; aquaculture; animal health; post-harvest
National Category
Clinical Medicine
Identifiers
urn:nbn:se:liu:diva-113485 (URN)10.1017/S1751731114002602 (DOI)000346585000001 ()25359324 (PubMedID)
Note

Funding Agencies|European Science Foundation (Brussels, Belgium)

Available from: 2015-01-19 Created: 2015-01-19 Last updated: 2017-12-05
Bayat, N., Lopes, V., Sanchez-Dominguez, M., Lakshmanan, R., Rajarao, G. K. & Cristobal, S. (2015). Assessment of functionalized iron oxide nanoparticles in vitro: introduction to integrated nanoimpact index. ENVIRONMENTAL SCIENCE-NANO, 2(4), 380-394
Open this publication in new window or tab >>Assessment of functionalized iron oxide nanoparticles in vitro: introduction to integrated nanoimpact index
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2015 (English)In: ENVIRONMENTAL SCIENCE-NANO, ISSN 2051-8153, Vol. 2, no 4, p. 380-394Article in journal (Refereed) Published
Abstract [en]

Functionalization of super paramagnetic iron oxide NPs (SPIONs) with different coatings renders them with unique physicochemical properties that allow them to be used in a broad range of applications such as drug targeting and water purification. However, it is required to fill the gap between the promises of any new functionalized SPIONs and the effects of these coatings on the NPs safety. Nanotoxicology is offering diverse strategies to assess the effect of exposure to SPIONs in a case-by-case manner but an integrated nanoimpact scale has not been developed yet. We have implemented the classical integrated biological response (IBR) into an integrated nanoimpact index (INI) as an early warning scale of nano-impact based on a combination of toxicological end points such as cell proliferation, oxidative stress, apoptosis and genotoxicity. Here, the effect of SPIONs functionalized with tri-sodium citrate (TSC), polyethylenimine (PEI), aminopropyl-triethoxysilane (APTES) and Chitosan (chitosan) were assessed on human keratinocytes and endothelial cells. Our results show that endothelial cells were more sensitive to exposure than keratinocytes and the initial cell culture density modulated the toxicity. PEI-SPIONs had the strongest effects in both cell types while TSC-SPIONS were the most biocompatible. This study emphasizes not only the importance of surface coatings but also the cell type and the initial cell density on the selection of toxicity assays. The INI developed here could offer an initial rationale to choose either modifying SPIONs properties to reduce its nanoimpact or performing a complete risk assessment to define the risk boundaries.

Place, publisher, year, edition, pages
Royal Society of Chemistry, 2015
National Category
Clinical Medicine
Identifiers
urn:nbn:se:liu:diva-120888 (URN)10.1039/c5en00016e (DOI)000358869200008 ()
Note

Funding Agencies|Swedish Research Council; Carl Trygger Foundation; VINNOVA; Oscar and Lilli Lamms Minne Foundation; IKERBASQUE, Basque Foundation for science; Angpanneforening Research foundation; ALF; LiU-support; Erasmus Mundus Cooperation Window (EURINDIA); NaNoTeCh; National Nanotechnology Laboratory of Mexico

Available from: 2015-08-28 Created: 2015-08-28 Last updated: 2017-02-20
Garcia-Sanchez, S., Bernales, I. & Cristobal, S. (2015). Early response to nanoparticles in the Arabidopsis transcriptome compromises plant defence and root-hair development through salicylic acid signalling. BMC Genomics, 16(341)
Open this publication in new window or tab >>Early response to nanoparticles in the Arabidopsis transcriptome compromises plant defence and root-hair development through salicylic acid signalling
2015 (English)In: BMC Genomics, ISSN 1471-2164, E-ISSN 1471-2164, Vol. 16, no 341Article in journal (Refereed) Published
Abstract [en]

Background: The impact of nano-scaled materials on photosynthetic organisms needs to be evaluated. Plants represent the largest interface between the environment and biosphere, so understanding how nanoparticles affect them is especially relevant for environmental assessments. Nanotoxicology studies in plants allude to quantum size effects and other properties specific of the nano-stage to explain increased toxicity respect to bulk compounds. However, gene expression profiles after exposure to nanoparticles and other sources of environmental stress have not been compared and the impact on plant defence has not been analysed. Results: Arabidopsis plants were exposed to TiO2-nanoparticles, Ag-nanoparticles, and multi-walled carbon nanotubes as well as different sources of biotic (microbial pathogens) or abiotic (saline, drought, or wounding) stresses. Changes in gene expression profiles and plant phenotypic responses were evaluated. Transcriptome analysis shows similarity of expression patterns for all plants exposed to nanoparticles and a low impact on gene expression compared to other stress inducers. Nanoparticle exposure repressed transcriptional responses to microbial pathogens, resulting in increased bacterial colonization during an experimental infection. Inhibition of root hair development and transcriptional patterns characteristic of phosphate starvation response were also observed. The exogenous addition of salicylic acid prevented some nano-specific transcriptional and phenotypic effects, including the reduction in root hair formation and the colonization of distal leaves by bacteria. Conclusions: This study integrates the effect of nanoparticles on gene expression with plant responses to major sources of environmental stress and paves the way to remediate the impact of these potentially damaging compounds through hormonal priming.

Place, publisher, year, edition, pages
BioMed Central, 2015
Keywords
Nanoparticles; Nanotoxycology; Arabidopsis; Defence; Transcriptome; Stress; Systemic acquired response
National Category
Clinical Medicine
Identifiers
urn:nbn:se:liu:diva-118243 (URN)10.1186/s12864-015-1530-4 (DOI)000353764800001 ()25903678 (PubMedID)
Note

Funding Agencies|Swedish Research Council-Natural Science (VR-N); Carl Trygger Foundation; VINNOVA-Vinnmer program, Linkoping University; ALF-funding from Ostgota Counties, Sweden; IKERBASQUE-Basque Foundation for Science, Spain

Available from: 2015-05-22 Created: 2015-05-22 Last updated: 2017-12-04
Helander, S., Montecchio, M., Pilstål, R., Su, Y., Kuruvilla, J., Johansson, M., . . . Sunnerhagen, M. (2015). Pre-Anchoring of Pin1 to Unphosphorylated c-Myc in a Fuzzy Complex Regulates c-Myc Activity. Structure, 23(12), 2267-2279
Open this publication in new window or tab >>Pre-Anchoring of Pin1 to Unphosphorylated c-Myc in a Fuzzy Complex Regulates c-Myc Activity
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2015 (English)In: Structure, ISSN 0969-2126, E-ISSN 1878-4186, Vol. 23, no 12, p. 2267-2279Article in journal (Refereed) Published
Abstract [en]

Hierarchic phosphorylation and concomitant Pin1-mediated proline isomerization of the oncoprotein c-Myc controls its cellular stability and activity. However, the molecular basis for Pin1 recognition and catalysis of c-Myc and other multisite, disordered substrates in cell regulation and disease is unclear. By nuclear magnetic resonance, surface plasmon resonance, and molecular modeling, we show that Pin1 subdomains jointly pre-anchor unphosphorylated c-Myc1–88 in the Pin1 interdomain cleft in a disordered, or “fuzzy”, complex at the herein named Myc Box 0 (MB0) conserved region N-terminal to the highly conserved Myc Box I (MBI). Ser62 phosphorylation in MBI intensifies previously transient MBI-Pin1 interactions in c-Myc1–88 binding, and increasingly engages Pin1PPIase and its catalytic region with maintained MB0 interactions. In cellular assays, MB0 mutated c-Myc shows decreased Pin1 interaction, increased protein half-life, but lowered rates of Myc-driven transcription and cell proliferation. We propose that dynamic Pin1 recognition of MB0 contributes to the regulation of c-Myc activity in cells

Place, publisher, year, edition, pages
Cell Press, 2015
National Category
Natural Sciences
Identifiers
urn:nbn:se:liu:diva-106184 (URN)10.1016/j.str.2015.10.010 (DOI)
Note

The previous status of this article was Manuscript and the original title was Pre-anchoring of Pin1 to unphosphorylated c-Myc in a dynamic complex affects c-Myc stability andactivity.

Funding Agencies|Knut and Alice Wallenberg Foundation; Swedish Cancer Foundation; Swedish Child Cancer Foundation; Carl Trygger foundation; LiU Cancer Research Network; Swedish Research Council; NCI [R01s CA129040, CA100855]

Available from: 2014-04-28 Created: 2014-04-28 Last updated: 2018-05-06Bibliographically approved
Organisations
Identifiers
ORCID iD: ORCID iD iconorcid.org/0000-0002-3894-2218

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